Eyesight to the Blind-Pharmacotherapy for Retinopathy of Prematurity

Abstract

Retinopathy of prematurity (ROP) places preterm infants at significant risk for blindness. Angiogenesis of retinal blood vessels relies on vascular endothelial growth factor (VEGF) released in response to physiologic in utero hypoxia. Relative hyperoxia and disruption in the supply of growth factors after preterm birth lead to cessation of normal vascular growth. Recovery of VEGF production after 32 weeks' postmenstrual age results in aberrant vascular growth, including the formation of fibrous scars with the potential to detach the retina. Ablation of aberrant vessels by mechanical or pharmacologic methods relies on timely diagnosis in the early stages of ROP. Mydriatic medications dilate the pupil to allow examination of the retina. Mydriasis is typically accomplished using a combination of topical phenylephrine, a potent alpha-receptor agonist, and cyclopentolate, an anticholinergic. Systemic absorption of these agents results in a high incidence of cardiovascular, gastrointestinal, and respiratory adverse effects. Procedural analgesia should include the topical anesthetic proparacaine, oral sucrose, and nonpharmacologic interventions like non-nutritive sucking. Analgesia is often incomplete, leading to investigation of systemic agents like oral acetaminophen. If ROP threatens retinal detachment, laser photocoagulation is utilized to arrest vascular growth. More recently, the VEGF-antagonists, bevacizumab and ranibizumab, have emerged as treatment options. Systemic absorption of intraocular bevacizumab and the profound consequences of diffuse disruption of VEGF in the setting of rapid, neonatal organogenesis require dose optimization and careful evaluation of long-term outcomes in clinical trials. Intraocular ranibizumab is likely a safer alternative; however, outstanding questions remain regarding efficacy. Optimal patient outcomes rely on a combination of risk management throughout neonatal intensive care, timely diagnosis through careful ophthalmologic examinations, and treatment when indicated with laser therapy and/or anti-VEGF intravitreal injection.

Keywords: bevacizumab; cyclopentolate; pharmacology; phenylephrine; proparacaine; retinopathy of prematurity.